We propose an interdisciplinary program to explore the integrated function of respiration and circulation at different levels of interaction. We attempt to show how mechanical stresses between lung tissue and pulmonary vessels influence pulmonary hemodynamics and pulmonary fluid exchange. Similarly, we explore how the mechanical stresses between the lungs, thorax, and heart influence both right and left ventricular performance and afterload. The mechanical interdependence between the lungs, pulmonary vessels, and heart plays a major role in the effect of spontaneous and artificial ventilation in the production and therapy of pulmonary edema. We have developed a number of special animal preparations to explore the possibility that the transport of oxygen between air and blood and between blood and tissue might involve facilitative diffusion through cytochrome P-450. We are examining the physiological effects of hypoxia, hypercapnia, and acidosis on the carotid and aortic bodies, the pulmonary and cerebral circulations, and cardiac and skeletal muscle. We are applying the concepts of waterfall hemodynamics to the coronary circulation. We believe that it shall be possible to detect coronary insufficiency under conditions where conventional resistance measurements would show no changes. The special circulatory and respiratory experimental preparations are being used to determine how immunological factors produce anaphylaxis and the optimal therapy for it.